Variation in the FFAR1 gene modifies BMI, body composition and beta-cell function in overweight subjects: an exploratory analysis

• Published in: PloS one 2011-04, Vol.6 (4), p.e19146-e19146
• Main Authors: Walker, Celia G, Goff, Louise, Bluck, Les J, Griffin, Bruce A, Jebb, Susan A, Lovegrove, Julie A, Sanders, Thomas A B, Frost, Gary S
• Format: Article
• Language: English
• Subjects: Adipocytes; Alleles; Analysis; Beta cells; Blood lipids; Body composition; Body Composition - genetics; Body fat; Body mass; Body Mass Index; Body weight; Central nervous system; Chains; Cholesterol; Cohort Studies; Composition effects; Diabetes; Diabetes mellitus; Diet; Fasting; Fatty acids; Female; G protein-coupled receptors; Genes; Glucose; Glucose Tolerance Test; Health risks; High density lipoprotein; Homeostasis; Humans; Insulin; Insulin - metabolism; Insulin resistance; Insulin Secretion; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Laboratories; Lipids; Lipids - blood; Low density lipoprotein; Low density lipoproteins; Male; Medicine; Metabolic syndrome; Middle Aged; Nutrition research; Obesity; Overweight; Overweight - blood; Overweight - genetics; Overweight - metabolism; Overweight - pathology; Pancreas; Pancreatic beta cells; Phenotyping; Physiological aspects; Polymorphism, Single Nucleotide; Proteins; Receptors, G-Protein-Coupled - genetics; Rodents; Sensitivity; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0019146

FFAR1 receptor is a long chain fatty acid G-protein coupled receptor which is expressed widely, but found in high density in the pancreas and central nervous system. It has been suggested that FFAR1 may play a role in insulin sensitivity, lipotoxicity and is associated with type 2 diabetes. Here we investigate the effect of three common SNPs of FFAR1 (rs2301151; rs16970264; rs1573611) on pancreatic function, BMI, body composition and plasma lipids. For this enquiry we used the baseline RISCK data, which provides a cohort of overweight subjects at increased cardiometabolic risk with detailed phenotyping. The key findings were SNPs of the FFAR1 gene region were associated with differences in body composition and lipids, and the effects of the 3 SNPs combined were cumulative on BMI, body composition and total cholesterol. The effects on BMI and body fat were predominantly mediated by rs1573611 (1.06 kg/m(2) higher (P = 0.009) BMI and 1.53% higher (P = 0.002) body fat per C allele). Differences in plasma lipids were also associated with the BMI-increasing allele of rs2301151 including higher total cholesterol (0.2 mmol/L per G allele, P = 0.01) and with the variant A allele of rs16970264 associated with lower total (0.3 mmol/L, P = 0.02) and LDL (0.2 mmol/L, P